Little is currently known about risk factors for the development of recurrent herpes labialis (RHL) following a primary herpes simplex (HSV) infection. The specific aim of the proposed epidemiology study is to investigate familial predisposition to RHL. A cross-sectional sample of 500 student blood donors will be tested for HSV-1 antibodies and interviewed of RHL histories and family composition. All family members identified will be contacted and queried on their own RHL history. Using multivariate analytic methods, RHL cases (seropositive subjects with positive RHL histories) will be compared to controls (seropositive subjects with negative RHL histories) on the prevalence of RHL among biologic and nonbiologic family members. Odds ratios and 95 percent confidence intervals will be calculated to test three familial predisposition hypotheses. In addition, a follow-up study will be initiated, whereby, subjects developing perioral lesions will be examied at the university's student health clinic. The follow-up will allow a validation of self-reported RHL and will result in a population-based cohort of diagnosed RHL subjects for further studies. The long-term goal of the proposed study is to develop a research program of recurrent oral and labial herpes epidemiology. RHL research is justified by the high prevalence (approximately 35%) of mild to severe disease and the prevalence of severe RHL is likely to become more significant with increased numbers of immunocompromized patients. Epidemiologic research leading to risk factor identification would significantly benefit implementation of advances in therapy and prevention. The results of this study will directly contribute to elucidation of the potential role of genetic factors in RHL susceptibility and will provide a base for the direction and design of further epidemiologic studies of RHL pathogenesis.